This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomer... See more...

Aliases for PI3 Gene

Aliases for PI3 Gene

  • Peptidase Inhibitor 3 2 3 4 5
  • Skin-Derived Antileukoproteinase 2 3 4
  • WFDC14 2 3 4
  • SKALP 2 3 4
  • WAP3 2 3 4
  • ESI 2 3 4
  • Protease Inhibitor 3, Skin-Derived (SKALP) 2 3
  • WAP Four-Disulfide Core Domain Protein 14 3 4
  • Peptidase Inhibitor 3, Skin-Derived 2 3
  • Elastase-Specific Inhibitor 3 4
  • Protease Inhibitor WAP3 3 4
  • Trappin-2 2 3
  • Cementoin 2 3
  • Elafin 3 4
  • PI-3 3 4
  • WAP Four-Disulfide Core Domain 14 3
  • Pre-Elafin 3
  • ELAFIN 2
  • PI3 5

External Ids for PI3 Gene

Previous GeneCards Identifiers for PI3 Gene

  • GC20P043531
  • GC20P044441
  • GC20P044489
  • GC20P044490
  • GC20P043236
  • GC20P043803
  • GC20P040545

Summaries for PI3 Gene

Entrez Gene Summary for PI3 Gene

  • This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. Expression of this gene is upgulated by bacterial lipopolysaccharides and cytokines. [provided by RefSeq, Oct 2014]

GeneCards Summary for PI3 Gene

PI3 (Peptidase Inhibitor 3) is a Protein Coding gene. Diseases associated with PI3 include Pustular Psoriasis and Impetigo Herpetiformis. Among its related pathways are Keratinization and Innate Immune System. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and peptidase inhibitor activity. An important paralog of this gene is SLPI.

UniProtKB/Swiss-Prot Summary for PI3 Gene

  • Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis. Has been shown to inhibit the alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic acetylcholine receptor and to produce a weak inhibition on Kv11.1/KCNH2/ERG1 and on the transient receptor potential cation channel subfamily V member 1 (TRPV1) (PubMed:29483648).

Gene Wiki entry for PI3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PI3 Gene

Genomics for PI3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PI3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20J045173 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 600.7 0.0 -36 2.7 CEBPB ZNF207 SMARCC2 JUN RCOR1 GTF2F1 JUND MAX DEK EP300 PI3 SLPI piR-31292-111 WFDC12
GH20J045832 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 5.1 +659.6 659639 4.3 BRCA1 CEBPG CREB1 ZBTB33 ATF7 PRDM10 ZNF629 IKZF1 KDM1A ZNF692 SNX21 TNNC2 WFDC3 CD40 PCIF1 NCOA5 SYS1 PI3 piR-37993 ACOT8
GH20J045811 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 4.9 +638.2 638196 3.4 SP1 HNRNPL CREB1 FOS LARP7 PRDM1 ZIC2 RBFOX2 POLR2A PATZ1 HSALNG0130426 UBE2C WFDC3 NCOA5 TP53RK DNTTIP1 WFDC13 PI3 SNX21
GH20J044698 Enhancer 0.5 FANTOM5 dbSUPER 4.7 -476.3 -476307 0.3 STAT1 TCF7L2 ADA PI3 PABPC1L KCNK15 ENSG00000132832 CCN5 KCNK15-AS1
GH20J045138 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 0.3 -36.2 -36202 1.3 CTCF JUND PKNOX1 REST NR2C1 RAD21 GABPA KLF9 CBX3 ZNF766 ENSG00000283142 LOC101929863 lnc-WFDC12-1 WFDC12 SLPI WFDC5 piR-43107-187 PI3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PI3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PI3

Top Transcription factor binding sites by QIAGEN in the PI3 gene promoter:
  • C/EBPbeta
  • GR
  • GR-alpha
  • GR-beta
  • NF-kappaB
  • NF-kappaB1
  • p53

Genomic Locations for PI3 Gene

Genomic Locations for PI3 Gene
chr20:45,174,902-45,176,544
(GRCh38/hg38)
Size:
1,643 bases
Orientation:
Plus strand
chr20:43,803,517-43,805,185
(GRCh37/hg19)
Size:
1,669 bases
Orientation:
Plus strand

Genomic View for PI3 Gene

Genes around PI3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PI3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PI3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PI3 Gene

Proteins for PI3 Gene

  • Protein details for PI3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P19957-ELAF_HUMAN
    Recommended name:
    Elafin
    Protein Accession:
    P19957
    Secondary Accessions:
    • E1P618
    • Q6FG74

    Protein attributes for PI3 Gene

    Size:
    117 amino acids
    Molecular mass:
    12270 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for PI3 Gene

neXtProt entry for PI3 Gene

Post-translational modifications for PI3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PI3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PI3 Gene

Domains & Families for PI3 Gene

Gene Families for PI3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for PI3 Gene

InterPro:
Blocks:
  • 4-disulphide core signature
ProtoNet:

Suggested Antigen Peptide Sequences for PI3 Gene

GenScript: Design optimal peptide antigens:
  • WAP four-disulfide core domain protein 14 (ELAF_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P19957

UniProtKB/Swiss-Prot:

ELAF_HUMAN :
  • Consists of two domains: the transglutaminase substrate domain (cementoin moiety) and the elastase inhibitor domain. The transglutaminase substrate domain serves as an anchor to localize elafin covalently to specific sites on extracellular matrix proteins.
Domain:
  • Consists of two domains: the transglutaminase substrate domain (cementoin moiety) and the elastase inhibitor domain. The transglutaminase substrate domain serves as an anchor to localize elafin covalently to specific sites on extracellular matrix proteins.
genes like me logo Genes that share domains with PI3: view

Function for PI3 Gene

Molecular function for PI3 Gene

UniProtKB/Swiss-Prot Function:
Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis. Has been shown to inhibit the alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic acetylcholine receptor and to produce a weak inhibition on Kv11.1/KCNH2/ERG1 and on the transient receptor potential cation channel subfamily V member 1 (TRPV1) (PubMed:29483648).
GENATLAS Biochemistry:
elafin,serine proteinase inhibitor,epidermal,member of the troppin family,induced in epidermis by cellular stress,involved in the regulation of inflammation and in protection against tissue damage,regulated by neutrophil elastase in type II alveolar epithelial cells

Phenotypes From GWAS Catalog for PI3 Gene

Gene Ontology (GO) - Molecular Function for PI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 2394696
GO:0004867 serine-type endopeptidase inhibitor activity TAS,IBA 21873635
GO:0030280 structural constituent of epidermis IDA 7543090
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with PI3: view
genes like me logo Genes that share phenotypes with PI3: view

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PI3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for PI3 Gene

Localization for PI3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PI3 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PI3 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 4
cytosol 4
endosome 3
lysosome 3
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001533 cornified envelope IDA,TAS --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005829 cytosol TAS --
GO:0031012 extracellular matrix TAS 8476637
genes like me logo Genes that share ontologies with PI3: view

Pathways & Interactions for PI3 Gene

genes like me logo Genes that share pathways with PI3: view

Gene Ontology (GO) - Biological Process for PI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007620 copulation IEA --
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0018149 peptide cross-linking IDA 7543090
GO:0019730 antimicrobial humoral response TAS --
genes like me logo Genes that share ontologies with PI3: view

No data available for SIGNOR curated interactions for PI3 Gene

Drugs & Compounds for PI3 Gene

(15) Drugs for PI3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) Additional Compounds for PI3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PI3: view

Transcripts for PI3 Gene

mRNA/cDNA for PI3 Gene

1 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PI3

Alternative Splicing Database (ASD) splice patterns (SP) for PI3 Gene

No ASD Table

Relevant External Links for PI3 Gene

GeneLoc Exon Structure for
PI3

Expression for PI3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PI3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PI3 Gene

This gene is overexpressed in Esophagus - Mucosa (x22.7), Vagina (x12.3), and Whole Blood (x7.6).

Protein differential expression in normal tissues from HIPED for PI3 Gene

This gene is overexpressed in Cervix (33.8) and Oral epithelium (20.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PI3 Gene



Protein tissue co-expression partners for PI3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PI3

SOURCE GeneReport for Unigene cluster for PI3 Gene:

Hs.112341

Evidence on tissue expression from TISSUES for PI3 Gene

  • Skin(4.7)
  • Nervous system(4.5)
  • Intestine(3.5)
  • Blood(3)
  • Lung(2.8)
  • Muscle(2.5)
  • Liver(2.4)
  • Spleen(2.3)
  • Heart(2.3)
  • Kidney(2.2)
  • Stomach(2.1)
  • Lymph node(2)
genes like me logo Genes that share expression patterns with PI3: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PI3 Gene

Orthologs for PI3 Gene

This gene was present in the common ancestor of mammals.

Orthologs for PI3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PI3 30 31
  • 100 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PI3 30 31
  • 76.95 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia -- 31
  • 50 (a)
OneToMany
-- 31
  • 48 (a)
OneToMany
-- 31
  • 45 (a)
OneToMany
PI3 31
  • 43 (a)
OneToMany
Species where no ortholog for PI3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Mouse (Mus musculus)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for PI3 Gene

ENSEMBL:
Gene Tree for PI3 (if available)
TreeFam:
Gene Tree for PI3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PI3: view image

Paralogs for PI3 Gene

Paralogs for PI3 Gene

genes like me logo Genes that share paralogs with PI3: view

Variants for PI3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PI3 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
rs761507163 Uncertain Significance: not provided 45,174,923(+) A/G INITIATIOR_CODON_VARIANT,MISSENSE_VARIANT
rs17333103 - p.Thr17Met
rs2664581 - p.Thr34Pro

Additional dbSNP identifiers (rs#s) for PI3 Gene

Structural Variations from Database of Genomic Variants (DGV) for PI3 Gene

Variant ID Type Subtype PubMed ID
nsv1056102 CNV loss 25217958

Variation tolerance for PI3 Gene

Residual Variation Intolerance Score: 76.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.03; 60.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PI3 Gene

Human Gene Mutation Database (HGMD)
PI3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PI3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PI3 Gene

Disorders for PI3 Gene

MalaCards: The human disease database

(21) MalaCards diseases for PI3 Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search PI3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PI3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PI3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PI3 Gene

Publications for PI3 Gene

  1. Genetic polymorphisms of peptidase inhibitor 3 (elafin) are associated with acute respiratory distress syndrome. (PMID: 19251943) Tejera P … Christiani DC (American journal of respiratory cell and molecular biology 2009) 3 23 41
  2. SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis. (PMID: 9727750) Kuijpers AL … Schalkwijk J (Clinical genetics 1998) 3 23 41
  3. Assignment of the human gene encoding the epidermal serine proteinase inhibitor SKALP (PI3) to chromosome region 20q12-->q13. (PMID: 8287685) Molhuizen HO … Schalkwijk J (Cytogenetics and cell genetics 1994) 2 3 23
  4. SKALP/elafin: an elastase inhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for transglutaminase cross-linking. (PMID: 7685029) Molhuizen HO … Schalkwijk J (The Journal of biological chemistry 1993) 3 4 23
  5. Characterization and gene sequence of the precursor of elafin, an elastase-specific inhibitor in bronchial secretions. (PMID: 8476637) Sallenave JM … Silva A (American journal of respiratory cell and molecular biology 1993) 3 4 23

Products for PI3 Gene

Sources for PI3 Gene